The long-range goals of this project are: (1) to evaluate the effects of prenatal exposure to hormonally active environmental chemicals on the subsequent reproductive capacity of the offspring; (2) to investigate the mechanisms involved in the production of subfertility in mammals as a result of their in utero exposure to foreign chemicals; (3) to assess the transplacental carcinogenic potential of these compounds; (4) to study the physiologic disposition and metabolism of these compounds in the pregnant animal and fetus; (5) to study chemico-biological interactions of transplacental toxicants, with special emphasis on structure-activity relationships; (6) to determine if prenatal exposure to environmental agents can alter the biological response to steroid hormones in reproductive tract tissues; (7) to develop and utilize organ and cell culture systems to study the effects of hormonally active environmental chemicals on the development of the fetal reproductive tract in vitro; (8) to study at the cellular and molecular levels alterations in genital tract differentiation induced by hormonally active compounds; and (9) to evaluate the above animal models as predictors of human response. Special attention is given to diethylstilbestrol (DES).